Program in Neuroscience, University of Fribourg, Switzerland
Dr. Jean-Luc Dreyer
Institute of Biochemistry
University of Fribourg
1700 FRIBOURG
SWITZERLAND
phone +41-26-300 8632
email Jean-Luc.Dreyer
Website
Molecular adaptations in the development of dopaminergic projections
Our long-term goal is to identify the molecular cues which govern the topographic organization of the midbrain dopaminergic pathway during development and behavioural adaptation. This pathway - which is well characterized anatomically and physiologically during development and at maturity - is implicated in several important functions (e.g., in the control of gonadal hormones, the autonomic nervous system and stress) and maladies (e.g., thought and affective disorders; tardive dyskinesia; and degenerative conditions, such as Parkinson's disease and Huntington's chorea). It also plays a key role in the reinforcement of behaviour, in reward, and in the development of psychological addiction to drugs such as cocaine, heroin, amphetamine and nicotine.
Topographic mapping during development is achieved by matching the gradients of chemoaffinity markers within presynaptic and postsynaptic neurones in anatomically related areas. Such chemoaffinity gradients have been observed in several systems, including the mesolimbic dopaminergic one. Together with G.Miescher, we wish to identify the guidance molecules which effect the adaptations in midbrain dopaminergic projections occurring during development and in association with behavioural changes. The molecular cues which guide neurones during the development of the central nervous system are re-expressed after challenge with psychomotor stimulants, and the almost imperceptible synaptic alterations thereby incurred may be brought to bear by the very molecular cues which direct the formation of the projection-target connections during development.
The molecular cues involved in these events are being identified in our laboratory by established molecular biological methodologies: amplification of mRNA from single cells, targeted differential display of mRNA (tDDRT-PCR), microarrays, cloning and reverse Northern-blot analysis. The genes identified in different behavioural protocols (acute and chronic drug treatment, drug withdrawal or drug sensitization) or at different developmental stages are functionally analyzed by means of in situ hydridization.
Selected publications
Yue Y. & Dreyer J.-L. Developmental Changes in the Localization of the Transplasma-Membrane NADH-Dehydrogenases in Rat Brain. Dev. Brain Res. 89: 253-263, 1995
Zurbriggen R. & Dreyer J.-L. The plasma membrane NADH-diaphorase is active during selective phases of the cell cycle in a mice neuroblastoma cell line NB41A3. Its relation to cell growth and differentiation. Biochim. Biophys. Acta 1312: 215-222, 1996
Yue Y., Widmer D., Cerretti D.P., Wagner G., Dreyer J.-L. & Renping Z. Specification of Distinct Dopaminergic Neural Pathways: Roles of the Eph Family Receptor EphB1 and Ligand Ephrin-B2. J.Neurosci. 19: 2090-2101, 1998